Tuesday, September 16, 2008

The DNA Network

The DNA Network

Kicking the "common disease/common variant hypothesis" while its down [biomarker-driven mental health 2.0]

Posted: 16 Sep 2008 07:13 PM CDT

Digital mock-up of human evolution display for...Image by Colin Purrington via Flickr

Just piling on to the many comments on today's NY Times profile of David Goldstein who justifiably points out a dearth of whole-genome-snp-scanning success. One interesting debate is whether natural selection had anything to do with expunging the much sought-after (impossible to find) deleterious, disorder-promoting variants (he suggests yes) which means that whilst separate human cultures adapted to separate climate, predators, diets etc. one might expect to identify separate genetic variants that define racial or cultural subgroups (he says no). Huh?

According to the article, Goldstein "says he thinks that no significant genetic differences will be found between races because of his belief in the efficiency of natural selection. Just as selection turns out to have pruned away most disease-causing variants, it has also maximized human cognitive capacities because these are so critical to survival. "My best guess is that human intelligence was always a helpful thing in most places and times and we have all been under strong selection to be as bright as we can be.""

We have a free and open article describing the relationship of a common variant in the COMT gene with human intelligence, which is also supported by a recent meta-analysis on COMT. These findings certainly do not refute Dr. Goldstein's conclusions, but rather make me wonder why the common valine/methionine variant in COMT might exert a tiny, but measurable, effect on intelligence. Balancing selection possibly ?

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Gene Genie #36 and #37 [ScienceRoll]

Posted: 16 Sep 2008 04:25 PM CDT

Because of my surgery exam, it was a bit hard to keep up with the latest editions:

The  36th edition is up at Human Genetics Disorders. A great compilation of articles and blogposts about human genetics and personalized medicine. Thank you, Chavonne Jones, for hosting Gene Genie.

The  37th edition is up at The Genetic Genealogist. A great compilation of articles and blogposts about human genetics and personalized medicine. Thank you, Blaine Bettinger, for hosting Gene Genie.

Gene Genie is the blog carnival of genes and gene-related diseases. Our plan is to cover the whole genome before 2082 (it means 14-15 genes every two weeks). We accept articles on the news of genomics and clinical genetics. The news and articles of personalized genetics are also included. Check out Gene Genie for more about this unique field of medicine.

Many thanks to Ricardo Vidal for the logo!

Next edition is due to be published on the 30st of September 2008. Don't forget to submit your articles via the official page.

Let me know if you would like to host an edition.

Here are all the issues of Gene genie:

Do schools kill creativity? [Mailund on the Internet]

Posted: 16 Sep 2008 02:18 PM CDT

Slightly on topic on the previous post on teaching:Sir Ken Robinson: Do schools kill creativity?

Teaching programming in bioinformatics [Mailund on the Internet]

Posted: 16 Sep 2008 01:44 PM CDT

Next term, I am teaching a class called applied programming, which is just a fancy title for script programming.

I finally got out of teaching programming a year or so ago.  I don’t really like to teach this topic.  I love programming, but I find it very hard to teach.  It is something you only learn by doing, and the typical university setup here is lectures.  That simply doesn’t work with programming classes. Period.

Anyway, the university has started a new bachelors program — molecular medicine — and they need to learn a lot of bioinformatics.  For that, they need some basic programming, and I have to teach them that together with Søren Besenbacher.

Teaching programming

In some sense, all skills you learn, you learn by “doing”.  Even if what you are doing is just thinking about it.

Asking students “to think about it” is not the way to go, though.  Trust me on that.

You need some techniques to start thinking.  If you discuss a topic with your friends — construct arguments for your case — you are forced to think about the topic.  If you have to present a topic to your class, you are forced to think about the topic.

When you teach a topic, you are really forced to think about it.

Programming, you really have to think about. You cannot fool the computer.  If you don’t know how to solve a problem, there is no bullshitting the computer into believing that you can.

So in a sense, it should be easy to teach programming. Give people a problem and let them solve it.  There is no cheating, and as long as the problem highlights the points you wish to teach, the students will learn it.

Why do I still find it hard to teach programming then?

Lecturing on programming

One problem is the way we typically teach here.  Teaching is very much based on lecturing followed by practical exercises with TAs.

It is mostly a practical matter. For practical exercises, you need small groups, and we would spend all our time on teaching if we had to do all the exercises ourselves.  Thus the TAs.  But you cannot leave the entire class to TAs and small groups, so we have the lectures to cover the broad topics and make sure that all the groups are keeping up with the teaching plan.

In many classes, this setup works fine, but I don’t think it helps much to lecture on programming.  The lectures in such a class can easily end up being a waste of time.

I can show you all the language constructs of Python on a PowerPoint slide, but that alone does nothing for teaching you how to use them.  It is absolutely worthless if you need to solve a problem using Python.

With 50+ students, I’m probably stuck with the lectures, but how do you structure lectures so you actually teach something useful for programming?

Teaching problem solving

Programming is, more than anything else, problem solving. So how do you teach people how to solve problems?  You show them how you do it yourself!

This is where it gets tricky, I think.  You are not showing people how you solve problems by writing down the problem and then the solution.  You need to show them how you think when you are making your way from problem to solution.  And you need to do it very slowly!

When you are experienced, you make leaps of intuition when you solve a problem.  You recognize something you have solved before and — probably without thinking about it — you immediately think of a solution that worked before.  It is very hard to avoid this.

You need to slow down when solving the problems.  You don’t want to dumb down, though!  You need to solve the problem without your experience, not without your wits. The students are less experienced, they are not stupid, and you won’t keep them interested if you are thinking slower than they are.

Ideally, you want the solutions you come up with this way to be the same you would come up with if you were using all your experience.  I personally hate it when text books come up with solutions you would never see in the real world, just because they haven’t introduced all the techniques you need to get the “right” solution; only enough to actually solve the problem, but in a roundabout and non-idiomatic way.

To avoid this, you need to come up with problems that not only can be solved with the techniques seen so far, but where the ideal solution only uses those techniques. I’m still trying to figure out how to do this…

Anyway, these are the ideas I am throwing around right now for how to approach lecturing on programming again.

Refusing to help (or “give them what they need, not what they want”)

So show you show the students how to solve a problem, and then you give them some problems to solve themselves.  This is where the TAs come into play.  The idea is that the students try to solve the problems themselves or in small groups, and then can meet with the other students in larger groups, maybe 15-20 people, together with a TA to discuss problems and solutions.

For small classes, I’ve been doing both the lecturing and the solution discussions.  My experiences here are not so pleasant.

First of all, it is very hard to get the students to actually try to solve the problems.  Not the computer scientists. In the previous script programming classes there were always a few computer scientists.  Those are already interested in programming and, to be fair, already know how to do it.  The non-computer science students rarely made an effort.

There is, of course, a major difference in being interested in programming and in considering programming a necessary tool for some other problem that is the real problem.

So there is a bigger problem in motivating the problems, but I don’t think that is the full story.

Once the students figure out that they can just show up at the meetings with the TA and then the TA will show them how to solve the problems they got stuck on, they will simply stop trying to solve anything themselves.  At the first sign of trouble, they just stop.  They do not try to work around the problems, or try to figure out why there is a problem in the first place.

This is probably the worst thing they can possibly do.  Programming is all about solving a larger problem by working around a bit pile of smaller problems.  You get stuck all the time, and need to get yourself “unstuck”.  With experience you will do this faster and faster, and often manage to avoid a lot of the small problems in the first place, but you need to get this experience by actually solving the small problems.

When people ask me how I would solve a given problem, I tend to tell them.  This makes me the worst TA ever in a situation like this.  I have tried and tried, with more success the older I’m getting, not to help too much.

It is essential that you don’t help a student who could actually solve the problem himself if he just worked a little harder and a little longer.  We learn from our own experience, not others.

What’s so special about programming in Bioinformatic?

What are we doing teaching programming anyway?

The Department of Computer Science teaches an introduction to programming class that is mandatory for half the student programs at the Faculty of Sciences.  So why do we have our own introductory programming class for bioinformatics (and related student programs)?

This is a good question, and there has been some debate over it. If only it wasn’t me who is supposed to teach the class, I would be a strong proponent for it ;)

Kidding aside, I do think there are strong arguments for having a different introductory programming class.

It is getting late, and I have a paper to read before going to bed, so I will leave  those arguments for another post, though.

Applied programming?

Well, I didn’t choose this title for the class.  I wanted script programming, but apparently that didn’t sound serious. Go figure.

Is this really why we sequenced the human genome? [adaptivecomplexity's column]

Posted: 16 Sep 2008 12:37 PM CDT

I usually like Nicolas Wade, but this very first sentence of a piece in this week's NY Times science section is not right:

The principal rationale for the $3 billion spent to decode the human genome was that it would enable the discovery of the variant genes that predispose people to common diseases like cancer and Alzheimer's.


RFF: red fluorescent fish [Bayblab]

Posted: 16 Sep 2008 12:18 PM CDT

On the upcoming podcast we explain amongst other things why the sea is blue and what happens to red light in water (subscribe to the rss to listen!). For depths over 10m red light is pretty much irrelevant to fish. There is no purpose to see it since it is largely absent, and therefore no value in displaying it. Or is there? Here is a paper in BMC ecology with some stunning pictures and an account of how actually not only are some fish red-fluorescent, but it is also a really good private communication solution:

"We here report that at least 32 reef fishes from 16 genera and 5 families show pronounced red fluorescence under natural, daytime conditions at depths where downwelling red light is virtually absent. Fluorescence was confirmed by extensive spectrometry in the laboratory. In most cases peak emission was around 600 nm and fluorescence was associated with guanine crystals, which thus far were known for their light reflecting properties only. Our data indicate that red fluorescence may function in a context of intraspecific communication. Fluorescence patterns were typically associated with the eyes or the head, varying substantially even between species of the same genus. Moreover red fluorescence was particularly strong in fins that are involved in intraspecific signalling. Finally, microspectrometry in one fluorescent goby, Eviota pellucida, showed a long-wave sensitivity that overlapped with its own red fluorescence, indicating that this species is capable of seeing its own fluorescence."

Not only is this cool in itself but it may be useful for us lab rats to use in imaging and microscopy as it would have different properties than RFP and current dyes.

Common Disease Common Variant Dead??? [The Gene Sherpa: Personalized Medicine and You]

Posted: 16 Sep 2008 11:54 AM CDT

I don't think so.....If that is true, I know a few comapnies out West that could have a problem..... Turns out the publicist for my friend's friend must have gotten him a sweet article in the New...

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Congratulations to Stanley Falkow, Microbiologist Extraordinaire and Lasker Winner [The Tree of Life]

Posted: 16 Sep 2008 11:53 AM CDT

Short one here as I am at a conference. Very happy to see Stan Falkow get a Lasker Award.
"The breadth and depth of Falkow's career is being recognized with the 2008 Lasker-Koshland Award for Special Achievement in Medical Science."
He is a great scientist but more importantly to me, he has an infectious (no pun intended) enthusiasm for science, microbiology, and life. For more detail, there is a really nice article in the Stanford Report about him and his career. Every time I interact with him (e.g., when I was a student at Stanford) I feel like I got a microbiology passion boost that lasted for years. And clearly he has had this effect on many many others. Congratulations to him for a well deserved award.

Caution - Maverick Scientist Ahead [The Tree of Life]

Posted: 16 Sep 2008 11:11 AM CDT

Interesting article on David Goldstein (a co-author of my Evolution textbook) in the New York Times Mostly, it is kind of portraying him as a "maverick" in genomics (Note - Nick Wade seems to specialize a bit in portraying scientists as mavericks -- think of Craig Venter). Maverick of course is a term that is being overused in the election in the US these days and Wade does not use it to describe Goldstein, but that is the gist. Even the title "A Dissenting Voice as the Genome Is Sifted to Fight Disease."

The key quote is
"There is absolutely no question," he said, "that for the whole hope of personalized medicine, the news has been just about as bleak as it could be.
He also sort of disses the HapMap project and related activities. Goldstein, who I went to grad. school with, certainly can be contrary. And I do not work on human genomics so I do not know how close to home his claims about the lack of utility of the HapMap. But I think his general feeling here is probably right. Human genomics, as with many other genomicy things, has been oversold by many of the practitioners. That does not mean it is not useful --- and Goldstein makes this point. It is just that we need to be careful (I think and it seems so does Goldstein) in making claims about what the benefits of something in genomics will be before we see the actual benefits.

Beauty is in the ventral striatum of the beholder [biomarker-driven mental health 2.0]

Posted: 16 Sep 2008 10:28 AM CDT

2nd third of 19th centuryImage via Wikipedia

You see a masterpiece while I see splatters of paint on a canvas. Why - in neural terms - do we see the same painting and feel so subjectively different ?

Understanding the neural crosstalk between visual inputs (the raw neural activity generated in the retina) and our complex internal states (needs, desires, fears etc.) of an organism is a research problem that is long on philosophy but rather difficult to address experimentally. Professors P. Read Montague and Brooks King-Casas provide a conceptual overview to how such neural crosstalk might be collected, analyzed and understood in terms of basic computational processes that underlie human decision making. In their article, "Efficient statistics, common currencies and the problem of reward-harvesting", [doi: 10.1016/j.tics.2007.10.002] they provide an historical review of some of the major conceptual frameworks and give examples of how basic research in the area of reinforcement learning (dopamine serves as a reinforcement signal since it is released in the ventral striatum when you get more than you were expecting) might serve as a core cellular mechanism underlying the inter-linking of incoming sensory information with internal states. Dr. Montague's book on decision making is also a fun experience & great introduction to the burgeoning area of neuroeconomics.

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Plus, he rides a motorcycle [genomeboy.com]

Posted: 16 Sep 2008 07:51 AM CDT


"There is absolutely no question," he said, "that for the whole hope of personalized medicine, the news has been just about as bleak as it could be."

The New York Times has a feature on population genomicist David Goldstein  that is well worth your time. David, I should say, is a friend and colleague. He’s not always the warmest and fuzziest guy in the world, and his worldview tends to be closely aligned with Eeyore’s. But he is funny, charismatic, engaging and one of the most brilliant people I’ve ever met. He’s right a lot more often than he’s wrong. I had the pleasure of doing some editing on his book, Jacob’s Legacy, which I heartily and objectively recommend (heh).

Oh brother there art though (Uh oh, my brother has a blog) [The Tree of Life]

Posted: 15 Sep 2008 09:58 PM CDT

Well, just in case people out there did not have enough trouble distinguishing my brother, Michael Eisen,  from me (me - UCD - him UCB, me microbial genome evolution, him drosophila and yeast genome evolution, me - OA fanatic PLoS Biology AEIC, him PLoS founder and board member, and so on), here comes a new thing to deal with.

Seems worth checking out.  First posts are 

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